The Food and Drug Administration has declined to approve the RNA interference (RNAi) therapeutic agent patisiran (Onpattro, Alnylam Pharmaceuticals) for treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, the company has announced.

ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has declined to approve the RNA interference (RNAi) therapeutic agent patisiran (Onpattro, Alnylam Pharmaceuticals) for treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, the company has announced.

ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has declined to approve the RNA interference (RNAi) therapeutic agent patisiran (Onpattro, Alnylam Pharmaceuticals) for treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, the company has announced.

ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.

A version of this article first appeared on Medscape.com.

Before he attended medical school, Thomas O’Connor, MD, had a not-very-well-kept secret: As a competitive powerlifter, he had used steroids to build strength.

Now an internist and clinical instructor of medicine at the University of Connecticut, Farmington, Dr. O’Connor’s practice focuses on the needs of men taking testosterone and other anabolic steroids – a group he feels is poorly understood and largely neglected by conventional medical care, perceptions borne out by a 2020 study of steroid users he helped conduct.

“They felt discriminated against, they did not feel comfortable working with their physicians, and they felt that the doctors did not know what they were doing,” Dr. O’Connor said in an interview. His patients often express anger and frustration with doctors they had seen previously.
 

Patients turning to home tests

Not surprisingly, then, many users of illegal anabolic-androgenic steroids (AAS) have adopted a DIY approach to monitoring the side effects of the drugs, turning to direct-to-consumer laboratory tests. Clients can order a panel of labs designed to screen for health conditions commonly associated with use of AAS, such as dyslipidemia, renal and hepatic dysfunction, polycythemia, thrombosis, and insulin resistance. The panels also include tests for levels of different hormones.

Sales of direct-to-consumer tests topped $3.6 billion in the United States in 2022 and are predicted to grow. Some of that spending is coming from people, mostly men, using illegally obtained steroids to build muscle. Although published data on the size of the bodybuilder market are unavailable, the Internet is a ready source of relatively inexpensive tests aimed at helping individuals monitor their health.  

While clinicians may have their doubts about allowing patients to pick and choose tests and interpret their results, proponents claim they empower consumers to take control of their health – and save themselves money in the process.

But a test panel designed to help the user monitor the effects of banned substances is a bit unnerving to many clinicians, including Dr. O’Connor.

“People using anabolic steroids should be aware of the health risks associated with such use and that laboratory analysis is an important step toward improving health outcomes,” he said, “I’m all about open education, but not self-diagnosis and treatment.” 

Testosterone and other AAS such as nandrolone, trenbolone, and boldenone are Schedule III controlled substances that have been banned by numerous athletic governing bodies. Yet recreational users can easily obtain them from online international pharmacies without a prescription. Should they be monitoring themselves for side effects?

A basic problem is that few primary care clinicians routinely ask their patients about the use of AAS or feel competent to manage the complications or withdrawal symptoms associated with the agents. And they may have no idea what the average AAS user looks like.

The American College of Sports Medicine updated its statement on the use of AAS in 2021. The statement warned of a growing new segment of users – up to 70% of people who take the drugs do so recreationally in pursuit of a more muscular appearance, rather than competitive athletes seeking enhanced performance.

The ACSM highlighted the syndrome of muscle dysmorphia, also known as “megarexia” or “bigorexia” (think of it as “reverse anorexia”), as a major risk factor for illicit use of AAS.

Stuart Phillips, PhD, professor and director of the department of kinesiology at McMaster University, Hamilton, Ont., coauthored the ACSM guidelines. 

“The prince in Snow White circa 1950s was a guy with nice hair,” said Dr. Phillips, pointing to a change in cultural expectations for the male body. “But then fast forward to the prince or hero in any other Disney movie recently – and the guy is jacked.”

Since the last guidelines were published in 1987, Dr. Phillips has seen some cultural shifts. Testosterone has gone from a banned substance no one talked about to a mainstream medical therapy for men with low androgen levels, as any television viewer of primetime sports can attest. “But the other thing that’s changed,” he added, “is that we’ve seen the proliferation of illicit anabolic steroid use solely for the purpose of aesthetics.”

As an adolescent medicine physician who specializes in eating disorders, Jason Nagata, MD, MSc, sees many young men in his practice who engage in different behaviors to increase their muscle mass – from exercising, consuming high protein diets or taking protein supplements, even injecting AAS.

“A third of teenage boys across the U.S. report they’re trying to gain weight to bulk up and gain muscle,” said Dr. Nagata, an associate professor of pediatrics at the University of California, San Francisco.

In a 2020 study published in JAMA Pediatrics, Dr. Nagata and colleagues found that use of legal performance-enhancing substances in young men aged 18-26 years was associated with a higher odds of using AAS 7 years later (adjusted odds ratio, 3.18; 95% confidence interval, 1.90-5.32). “Some of the legal performance-enhancing substances like the protein powders or creatine may serve as a gateway to use of AAS,” Dr. Nagata said.  

Another important factor is exposure to AAS use on social media, where muscular influencers gain huge followings. Dr. Nagata said most of the research on eating disorders and social media has examined the role of media on weight loss in girls.

“Although there’s less research on the social media impact on boys and men, a few studies have shown links between more Instagram use and muscle dissatisfaction, as well as thinking about using steroids,” he said.

The number of people using AAS is not trivial. In a longitudinal study (led by Nagata) of young U.S. adults surveyed multiple times between 1994 and 2002, a total of 2.7% of 18- to 26-year-old men and 0.4% of women reported using AAS. In a more recent cohort of adolescents in Minnesota aged 14-22 years followed between 2010 and 2018, a total of 2.2% of males and 1% of females initiated AAS use. 

The Endocrine Society has estimated that between 2.9 and 4 million Americans have used an AAS at some point in their lives. Given that use is illegal without a prescription, a limitation of any survey is that participants may not be willing to disclose their AAS habit, leading to an underestimate of the actual number.

Nor are the complications of AAS use negligible. The drugs can have wide-ranging effects on the body, potentially affecting the brain, heart, liver, kidneys, musculoskeletal system, immune system, and reproductive systems. And individuals might unknowingly expose themselves to AAS: A recent literature review found that over a quarter of dietary supplements tested were found to contain undeclared substances that are on the World Anti-Doping Agency’s list of banned agents.
 

Alarming mistrust of MDs

Dr. O’Connor’s study shed some light on why AAS users might resort to surfing the Internet looking for a way to diagnose their own complications from steroid use. The web-based survey of nearly 2,400 men who said they took the drugs found that participants considered physicians to be the worst source of information, ranking them below coaches, online bodybuilding forums and sites, other AAS users, and bodybuilding books or magazines. The majority (56%) did not reveal AAS use to their clinicians. Of those who did, 55% reported feeling discriminated against for the admission.

Dr. O’Connor said physicians receive scant education on the many different drugs and regimens used by bodybuilders and have no idea how to a manage withdrawal syndrome for people trying to get off steroids. He urged the medical community to develop an educational campaign for clinicians, similar to those from public health officials aimed at combating the opioid epidemic: “Let’s educate med students and the residents. Let’s put [steroid use] on our agenda.”
 

Consumer testing evangelist ... or physician nemesis?

Nelson Vergel, BSChE, MBA, is on a mission to make medical lab testing affordable and accessible to everyone. The chemical engineer founded Discounted Labs 8 years ago, offering commonly ordered tests, such as complete blood counts, liver function tests, and cholesterol levels.

Mr. Vergel has advocated for the use of hormones to treat HIV-wasting disease for nearly 40 years, after his own diagnosis of the infection in 1986. After losing 40 pounds, steroids saved his life, he said.

Mr. Vergel said he was shocked to learn about the lack of continuing medical education on AAS for physicians and agreed with Dr. O’Connor that more training is needed for the medical profession. He also recognized that stigma on the part of clinicians is a huge barrier for many AAS users.

“We have to accept the fact that people are using them instead of demonizing them,” Mr. Vergel said. “What I was seeing is that there was so much stigma – and patients would not even talk to their doctors about their use.”

After reviewing Google analytics for his lab’s website and seeing how often “bodybuilder” came up as a search term, he added a panel of labs a year ago that allows AAS users to monitor themselves for adverse events.

Although he doesn’t condone the use of AAS without a medical indication and advises customers to discuss their results with a doctor, “we have to make sure people are reducing their harm or risk,” he said. “That’s really my goal.”

Many health care professionals would disagree with that statement. Dr. Nagata said he was concerned that management of side effects is too complicated. “There are a lot of nuances in the interpretation of these tests.” Arriving at the correct interpretation of the results requires a clinician’s thorough review of each patient’s health history, family history, and mental health history along with lab results. 
 

‘I’m concerned’

In a second article outlining harm-reduction strategies designed to improve care for patients using AAS, Dr. O’Connor and colleagues outlined an approach for talking with patients who are concerned about their health and are seeking guidance from a clinician.

The first step is to work on developing a rapport, and not to demand that patients stop their use of AAS. His recommended opening line is: “I want to be honest with you – I’m concerned.”

The initial interaction is an opportunity to find out why the person uses AAS, what health concerns they have at present, and why they are seeking care. Open-ended questions may reveal concerns that the patient has about fertility or side effects.

Consistent with harm-reduction approaches used for other public health epidemics – such as opioid abuse and blood-borne pathogens among people who inject drugs – follow-up visits can include nonjudgmental discussions about decreasing or stopping their use.

Ultimately, minimizing the harms of AAS use can serve as a bridge to their cessation, but the medical community needs to build up trust with a community of users who currently rely more on each other and the Internet for guidance than their primary care physicians. “We need more education. We’re going to need resources to do it,” Dr. O’Connell said. “And we’re going to have to do it.”

Dr. Phillips and Dr. Nagata have no financial disclosures. Mr. Vergel is the owner and founder of Discounted Labs but reported no other financial conflicts. Dr. O’Connor owns Anabolic Doc but has no additional financial disclosures.

A version of this article first appeared on Medscape.com.

Before he attended medical school, Thomas O’Connor, MD, had a not-very-well-kept secret: As a competitive powerlifter, he had used steroids to build strength.

Now an internist and clinical instructor of medicine at the University of Connecticut, Farmington, Dr. O’Connor’s practice focuses on the needs of men taking testosterone and other anabolic steroids – a group he feels is poorly understood and largely neglected by conventional medical care, perceptions borne out by a 2020 study of steroid users he helped conduct.

“They felt discriminated against, they did not feel comfortable working with their physicians, and they felt that the doctors did not know what they were doing,” Dr. O’Connor said in an interview. His patients often express anger and frustration with doctors they had seen previously.
 

Patients turning to home tests

Not surprisingly, then, many users of illegal anabolic-androgenic steroids (AAS) have adopted a DIY approach to monitoring the side effects of the drugs, turning to direct-to-consumer laboratory tests. Clients can order a panel of labs designed to screen for health conditions commonly associated with use of AAS, such as dyslipidemia, renal and hepatic dysfunction, polycythemia, thrombosis, and insulin resistance. The panels also include tests for levels of different hormones.

Sales of direct-to-consumer tests topped $3.6 billion in the United States in 2022 and are predicted to grow. Some of that spending is coming from people, mostly men, using illegally obtained steroids to build muscle. Although published data on the size of the bodybuilder market are unavailable, the Internet is a ready source of relatively inexpensive tests aimed at helping individuals monitor their health.  

While clinicians may have their doubts about allowing patients to pick and choose tests and interpret their results, proponents claim they empower consumers to take control of their health – and save themselves money in the process.

But a test panel designed to help the user monitor the effects of banned substances is a bit unnerving to many clinicians, including Dr. O’Connor.

“People using anabolic steroids should be aware of the health risks associated with such use and that laboratory analysis is an important step toward improving health outcomes,” he said, “I’m all about open education, but not self-diagnosis and treatment.” 

Testosterone and other AAS such as nandrolone, trenbolone, and boldenone are Schedule III controlled substances that have been banned by numerous athletic governing bodies. Yet recreational users can easily obtain them from online international pharmacies without a prescription. Should they be monitoring themselves for side effects?

A basic problem is that few primary care clinicians routinely ask their patients about the use of AAS or feel competent to manage the complications or withdrawal symptoms associated with the agents. And they may have no idea what the average AAS user looks like.

The American College of Sports Medicine updated its statement on the use of AAS in 2021. The statement warned of a growing new segment of users – up to 70% of people who take the drugs do so recreationally in pursuit of a more muscular appearance, rather than competitive athletes seeking enhanced performance.

The ACSM highlighted the syndrome of muscle dysmorphia, also known as “megarexia” or “bigorexia” (think of it as “reverse anorexia”), as a major risk factor for illicit use of AAS.

Stuart Phillips, PhD, professor and director of the department of kinesiology at McMaster University, Hamilton, Ont., coauthored the ACSM guidelines. 

“The prince in Snow White circa 1950s was a guy with nice hair,” said Dr. Phillips, pointing to a change in cultural expectations for the male body. “But then fast forward to the prince or hero in any other Disney movie recently – and the guy is jacked.”

Since the last guidelines were published in 1987, Dr. Phillips has seen some cultural shifts. Testosterone has gone from a banned substance no one talked about to a mainstream medical therapy for men with low androgen levels, as any television viewer of primetime sports can attest. “But the other thing that’s changed,” he added, “is that we’ve seen the proliferation of illicit anabolic steroid use solely for the purpose of aesthetics.”

As an adolescent medicine physician who specializes in eating disorders, Jason Nagata, MD, MSc, sees many young men in his practice who engage in different behaviors to increase their muscle mass – from exercising, consuming high protein diets or taking protein supplements, even injecting AAS.

“A third of teenage boys across the U.S. report they’re trying to gain weight to bulk up and gain muscle,” said Dr. Nagata, an associate professor of pediatrics at the University of California, San Francisco.

In a 2020 study published in JAMA Pediatrics, Dr. Nagata and colleagues found that use of legal performance-enhancing substances in young men aged 18-26 years was associated with a higher odds of using AAS 7 years later (adjusted odds ratio, 3.18; 95% confidence interval, 1.90-5.32). “Some of the legal performance-enhancing substances like the protein powders or creatine may serve as a gateway to use of AAS,” Dr. Nagata said.  

Another important factor is exposure to AAS use on social media, where muscular influencers gain huge followings. Dr. Nagata said most of the research on eating disorders and social media has examined the role of media on weight loss in girls.

“Although there’s less research on the social media impact on boys and men, a few studies have shown links between more Instagram use and muscle dissatisfaction, as well as thinking about using steroids,” he said.

The number of people using AAS is not trivial. In a longitudinal study (led by Nagata) of young U.S. adults surveyed multiple times between 1994 and 2002, a total of 2.7% of 18- to 26-year-old men and 0.4% of women reported using AAS. In a more recent cohort of adolescents in Minnesota aged 14-22 years followed between 2010 and 2018, a total of 2.2% of males and 1% of females initiated AAS use. 

The Endocrine Society has estimated that between 2.9 and 4 million Americans have used an AAS at some point in their lives. Given that use is illegal without a prescription, a limitation of any survey is that participants may not be willing to disclose their AAS habit, leading to an underestimate of the actual number.

Nor are the complications of AAS use negligible. The drugs can have wide-ranging effects on the body, potentially affecting the brain, heart, liver, kidneys, musculoskeletal system, immune system, and reproductive systems. And individuals might unknowingly expose themselves to AAS: A recent literature review found that over a quarter of dietary supplements tested were found to contain undeclared substances that are on the World Anti-Doping Agency’s list of banned agents.
 

Alarming mistrust of MDs

Dr. O’Connor’s study shed some light on why AAS users might resort to surfing the Internet looking for a way to diagnose their own complications from steroid use. The web-based survey of nearly 2,400 men who said they took the drugs found that participants considered physicians to be the worst source of information, ranking them below coaches, online bodybuilding forums and sites, other AAS users, and bodybuilding books or magazines. The majority (56%) did not reveal AAS use to their clinicians. Of those who did, 55% reported feeling discriminated against for the admission.

Dr. O’Connor said physicians receive scant education on the many different drugs and regimens used by bodybuilders and have no idea how to a manage withdrawal syndrome for people trying to get off steroids. He urged the medical community to develop an educational campaign for clinicians, similar to those from public health officials aimed at combating the opioid epidemic: “Let’s educate med students and the residents. Let’s put [steroid use] on our agenda.”
 

Consumer testing evangelist ... or physician nemesis?

Nelson Vergel, BSChE, MBA, is on a mission to make medical lab testing affordable and accessible to everyone. The chemical engineer founded Discounted Labs 8 years ago, offering commonly ordered tests, such as complete blood counts, liver function tests, and cholesterol levels.

Mr. Vergel has advocated for the use of hormones to treat HIV-wasting disease for nearly 40 years, after his own diagnosis of the infection in 1986. After losing 40 pounds, steroids saved his life, he said.

Mr. Vergel said he was shocked to learn about the lack of continuing medical education on AAS for physicians and agreed with Dr. O’Connor that more training is needed for the medical profession. He also recognized that stigma on the part of clinicians is a huge barrier for many AAS users.

“We have to accept the fact that people are using them instead of demonizing them,” Mr. Vergel said. “What I was seeing is that there was so much stigma – and patients would not even talk to their doctors about their use.”

After reviewing Google analytics for his lab’s website and seeing how often “bodybuilder” came up as a search term, he added a panel of labs a year ago that allows AAS users to monitor themselves for adverse events.

Although he doesn’t condone the use of AAS without a medical indication and advises customers to discuss their results with a doctor, “we have to make sure people are reducing their harm or risk,” he said. “That’s really my goal.”

Many health care professionals would disagree with that statement. Dr. Nagata said he was concerned that management of side effects is too complicated. “There are a lot of nuances in the interpretation of these tests.” Arriving at the correct interpretation of the results requires a clinician’s thorough review of each patient’s health history, family history, and mental health history along with lab results. 
 

‘I’m concerned’

In a second article outlining harm-reduction strategies designed to improve care for patients using AAS, Dr. O’Connor and colleagues outlined an approach for talking with patients who are concerned about their health and are seeking guidance from a clinician.

The first step is to work on developing a rapport, and not to demand that patients stop their use of AAS. His recommended opening line is: “I want to be honest with you – I’m concerned.”

The initial interaction is an opportunity to find out why the person uses AAS, what health concerns they have at present, and why they are seeking care. Open-ended questions may reveal concerns that the patient has about fertility or side effects.

Consistent with harm-reduction approaches used for other public health epidemics – such as opioid abuse and blood-borne pathogens among people who inject drugs – follow-up visits can include nonjudgmental discussions about decreasing or stopping their use.

Ultimately, minimizing the harms of AAS use can serve as a bridge to their cessation, but the medical community needs to build up trust with a community of users who currently rely more on each other and the Internet for guidance than their primary care physicians. “We need more education. We’re going to need resources to do it,” Dr. O’Connell said. “And we’re going to have to do it.”

Dr. Phillips and Dr. Nagata have no financial disclosures. Mr. Vergel is the owner and founder of Discounted Labs but reported no other financial conflicts. Dr. O’Connor owns Anabolic Doc but has no additional financial disclosures.

A version of this article first appeared on Medscape.com.

Before he attended medical school, Thomas O’Connor, MD, had a not-very-well-kept secret: As a competitive powerlifter, he had used steroids to build strength.

Now an internist and clinical instructor of medicine at the University of Connecticut, Farmington, Dr. O’Connor’s practice focuses on the needs of men taking testosterone and other anabolic steroids – a group he feels is poorly understood and largely neglected by conventional medical care, perceptions borne out by a 2020 study of steroid users he helped conduct.

“They felt discriminated against, they did not feel comfortable working with their physicians, and they felt that the doctors did not know what they were doing,” Dr. O’Connor said in an interview. His patients often express anger and frustration with doctors they had seen previously.
 

Patients turning to home tests

Not surprisingly, then, many users of illegal anabolic-androgenic steroids (AAS) have adopted a DIY approach to monitoring the side effects of the drugs, turning to direct-to-consumer laboratory tests. Clients can order a panel of labs designed to screen for health conditions commonly associated with use of AAS, such as dyslipidemia, renal and hepatic dysfunction, polycythemia, thrombosis, and insulin resistance. The panels also include tests for levels of different hormones.

Sales of direct-to-consumer tests topped $3.6 billion in the United States in 2022 and are predicted to grow. Some of that spending is coming from people, mostly men, using illegally obtained steroids to build muscle. Although published data on the size of the bodybuilder market are unavailable, the Internet is a ready source of relatively inexpensive tests aimed at helping individuals monitor their health.  

While clinicians may have their doubts about allowing patients to pick and choose tests and interpret their results, proponents claim they empower consumers to take control of their health – and save themselves money in the process.

But a test panel designed to help the user monitor the effects of banned substances is a bit unnerving to many clinicians, including Dr. O’Connor.

“People using anabolic steroids should be aware of the health risks associated with such use and that laboratory analysis is an important step toward improving health outcomes,” he said, “I’m all about open education, but not self-diagnosis and treatment.” 

Testosterone and other AAS such as nandrolone, trenbolone, and boldenone are Schedule III controlled substances that have been banned by numerous athletic governing bodies. Yet recreational users can easily obtain them from online international pharmacies without a prescription. Should they be monitoring themselves for side effects?

A basic problem is that few primary care clinicians routinely ask their patients about the use of AAS or feel competent to manage the complications or withdrawal symptoms associated with the agents. And they may have no idea what the average AAS user looks like.

The American College of Sports Medicine updated its statement on the use of AAS in 2021. The statement warned of a growing new segment of users – up to 70% of people who take the drugs do so recreationally in pursuit of a more muscular appearance, rather than competitive athletes seeking enhanced performance.

The ACSM highlighted the syndrome of muscle dysmorphia, also known as “megarexia” or “bigorexia” (think of it as “reverse anorexia”), as a major risk factor for illicit use of AAS.

Stuart Phillips, PhD, professor and director of the department of kinesiology at McMaster University, Hamilton, Ont., coauthored the ACSM guidelines. 

“The prince in Snow White circa 1950s was a guy with nice hair,” said Dr. Phillips, pointing to a change in cultural expectations for the male body. “But then fast forward to the prince or hero in any other Disney movie recently – and the guy is jacked.”

Since the last guidelines were published in 1987, Dr. Phillips has seen some cultural shifts. Testosterone has gone from a banned substance no one talked about to a mainstream medical therapy for men with low androgen levels, as any television viewer of primetime sports can attest. “But the other thing that’s changed,” he added, “is that we’ve seen the proliferation of illicit anabolic steroid use solely for the purpose of aesthetics.”

As an adolescent medicine physician who specializes in eating disorders, Jason Nagata, MD, MSc, sees many young men in his practice who engage in different behaviors to increase their muscle mass – from exercising, consuming high protein diets or taking protein supplements, even injecting AAS.

“A third of teenage boys across the U.S. report they’re trying to gain weight to bulk up and gain muscle,” said Dr. Nagata, an associate professor of pediatrics at the University of California, San Francisco.

In a 2020 study published in JAMA Pediatrics, Dr. Nagata and colleagues found that use of legal performance-enhancing substances in young men aged 18-26 years was associated with a higher odds of using AAS 7 years later (adjusted odds ratio, 3.18; 95% confidence interval, 1.90-5.32). “Some of the legal performance-enhancing substances like the protein powders or creatine may serve as a gateway to use of AAS,” Dr. Nagata said.  

Another important factor is exposure to AAS use on social media, where muscular influencers gain huge followings. Dr. Nagata said most of the research on eating disorders and social media has examined the role of media on weight loss in girls.

“Although there’s less research on the social media impact on boys and men, a few studies have shown links between more Instagram use and muscle dissatisfaction, as well as thinking about using steroids,” he said.

The number of people using AAS is not trivial. In a longitudinal study (led by Nagata) of young U.S. adults surveyed multiple times between 1994 and 2002, a total of 2.7% of 18- to 26-year-old men and 0.4% of women reported using AAS. In a more recent cohort of adolescents in Minnesota aged 14-22 years followed between 2010 and 2018, a total of 2.2% of males and 1% of females initiated AAS use. 

The Endocrine Society has estimated that between 2.9 and 4 million Americans have used an AAS at some point in their lives. Given that use is illegal without a prescription, a limitation of any survey is that participants may not be willing to disclose their AAS habit, leading to an underestimate of the actual number.

Nor are the complications of AAS use negligible. The drugs can have wide-ranging effects on the body, potentially affecting the brain, heart, liver, kidneys, musculoskeletal system, immune system, and reproductive systems. And individuals might unknowingly expose themselves to AAS: A recent literature review found that over a quarter of dietary supplements tested were found to contain undeclared substances that are on the World Anti-Doping Agency’s list of banned agents.
 

Alarming mistrust of MDs

Dr. O’Connor’s study shed some light on why AAS users might resort to surfing the Internet looking for a way to diagnose their own complications from steroid use. The web-based survey of nearly 2,400 men who said they took the drugs found that participants considered physicians to be the worst source of information, ranking them below coaches, online bodybuilding forums and sites, other AAS users, and bodybuilding books or magazines. The majority (56%) did not reveal AAS use to their clinicians. Of those who did, 55% reported feeling discriminated against for the admission.

Dr. O’Connor said physicians receive scant education on the many different drugs and regimens used by bodybuilders and have no idea how to a manage withdrawal syndrome for people trying to get off steroids. He urged the medical community to develop an educational campaign for clinicians, similar to those from public health officials aimed at combating the opioid epidemic: “Let’s educate med students and the residents. Let’s put [steroid use] on our agenda.”
 

Consumer testing evangelist ... or physician nemesis?

Nelson Vergel, BSChE, MBA, is on a mission to make medical lab testing affordable and accessible to everyone. The chemical engineer founded Discounted Labs 8 years ago, offering commonly ordered tests, such as complete blood counts, liver function tests, and cholesterol levels.

Mr. Vergel has advocated for the use of hormones to treat HIV-wasting disease for nearly 40 years, after his own diagnosis of the infection in 1986. After losing 40 pounds, steroids saved his life, he said.

Mr. Vergel said he was shocked to learn about the lack of continuing medical education on AAS for physicians and agreed with Dr. O’Connor that more training is needed for the medical profession. He also recognized that stigma on the part of clinicians is a huge barrier for many AAS users.

“We have to accept the fact that people are using them instead of demonizing them,” Mr. Vergel said. “What I was seeing is that there was so much stigma – and patients would not even talk to their doctors about their use.”

After reviewing Google analytics for his lab’s website and seeing how often “bodybuilder” came up as a search term, he added a panel of labs a year ago that allows AAS users to monitor themselves for adverse events.

Although he doesn’t condone the use of AAS without a medical indication and advises customers to discuss their results with a doctor, “we have to make sure people are reducing their harm or risk,” he said. “That’s really my goal.”

Many health care professionals would disagree with that statement. Dr. Nagata said he was concerned that management of side effects is too complicated. “There are a lot of nuances in the interpretation of these tests.” Arriving at the correct interpretation of the results requires a clinician’s thorough review of each patient’s health history, family history, and mental health history along with lab results. 
 

‘I’m concerned’

In a second article outlining harm-reduction strategies designed to improve care for patients using AAS, Dr. O’Connor and colleagues outlined an approach for talking with patients who are concerned about their health and are seeking guidance from a clinician.

The first step is to work on developing a rapport, and not to demand that patients stop their use of AAS. His recommended opening line is: “I want to be honest with you – I’m concerned.”

The initial interaction is an opportunity to find out why the person uses AAS, what health concerns they have at present, and why they are seeking care. Open-ended questions may reveal concerns that the patient has about fertility or side effects.

Consistent with harm-reduction approaches used for other public health epidemics – such as opioid abuse and blood-borne pathogens among people who inject drugs – follow-up visits can include nonjudgmental discussions about decreasing or stopping their use.

Ultimately, minimizing the harms of AAS use can serve as a bridge to their cessation, but the medical community needs to build up trust with a community of users who currently rely more on each other and the Internet for guidance than their primary care physicians. “We need more education. We’re going to need resources to do it,” Dr. O’Connell said. “And we’re going to have to do it.”

Dr. Phillips and Dr. Nagata have no financial disclosures. Mr. Vergel is the owner and founder of Discounted Labs but reported no other financial conflicts. Dr. O’Connor owns Anabolic Doc but has no additional financial disclosures.

A version of this article first appeared on Medscape.com.

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO—A new report offers a picture of patients seeking care for breast and gynecological cancers within the US Department of Veterans Affairs (VA) health care system: They are somewhat younger than their counterparts in the general population, and those with breast cancer are much more likely to be men.

            It is not clear whether these numbers are purely a reflection of the unique population within the VA or whether there is a more complicated explanation. Researchers also found that more than half of those with newly diagnosed breast, cervical, and ovarian cancers lived in the South compared with few (8%-13%) who lived in the Northeast.

The study findings were released in a poster at the 2023 annual meeting of the Association of VA Hematology/Oncology. Sarah Colonna, MD, study coauthor and medical director of breast oncology for the national VA, said in an interview that it is important to understand statistics regarding breast and gynecological cancer within the VA, especially as the system focuses more on patients with the conditions. And, she said, the wave of women who joined the military in recent decades are getting older and more likely to need oncology care. “We know women veterans are coming: They’re aging, and they’re going to get cancer.”

Colonna and colleagues examined statistics from the VA Corporate Data Warehouse to determine how many veterans were newly diagnosed with breast, uterine, ovarian, cervical, and vulvovaginal cancer in 2021 and 2022. The researchers compared their findings with 2020 statistics about the general population from the SEER database.

Within the VA, there were 3304 cases of breast cancer (mean age, 59 years; range, 23-99; mean body mass index [BMI], 31), 344 cases of cervical cancer (mean age, 46 years; range, 22-90; mean BMI, 29), 177 cases of ovarian cancer (mean age, 57 years; range, 24-80; mean BMI, 29), 365 cases of uterine cancer (mean age, 60 years; range, 24-85; mean BMI, 35), and 32 cases of vaginal/vulvar cancer (mean age, 56 years; range, 24-75; mean BMI, 31).

In contrast, the mean ages at diagnosis for the general population were slightly higher at 63 years for breast cancer, 50 years for cervical cancer, 63 years for ovarian cancer, and 63 years for uterine cancer. Vaginal/vulvar cancer was a bit of an outlier at mean age 69 years for the general population vs 56 years for the VA population; however, the number of cases in the latter group was quite low at 32 patients.

Overall, gynecological cancers were diagnosed at an average age of 55 years among the VA population vs 61 years among the general population. Men made up 11% of breast cancer cases in the VA vs 1% in the general population. “Of course, we have 10 times the proportion of men than in the outside,” said Colonna, an oncologist with the Huntsman Cancer Institute/Wahlen VA Medical Center in Utah. That may explain the difference, “but nobody knows for sure,” she said.

Patients Within the VA with the following cancers were more likely to be Black veterans than in the general population: breast, 30% vs 12%; cervical, 20% vs 14%; ovarian, 28% vs 10%; uterine, 25% vs 12%; and vaginal/vulvar, 44% vs 10%. This could reflect the fact that 30% of women treated within the VA are Black women vs 12% in the general population, Colonna said. Unfortunately, she said, “black women with breast cancer, tend to do really poorly. They tend to get it young, and they tend to die.”

As for the geographic distribution of cases, Colonna said it represents the high numbers of veterans who live in the South, suggesting that more VA oncology resources may be needed there.

In an interview, Aditi Hazra, PhD, MPH, an assistant professor of medicine at Harvard Medical School, said the new analysis is “very valuable”: “Women are a growing proportion of the veterans who serve, and we need more data to understand the risk factors and incidents of disease in this population.” Hazra said the next step will be to control the data for risk factors and “tease out what is driving the rates in the VA.”

There is no study funding, and the authors have no disclosures. Dr. Hazra discloses that she works for the VA and has collaborated with one of the study authors. 

CHICAGO—A new report offers a picture of patients seeking care for breast and gynecological cancers within the US Department of Veterans Affairs (VA) health care system: They are somewhat younger than their counterparts in the general population, and those with breast cancer are much more likely to be men.

            It is not clear whether these numbers are purely a reflection of the unique population within the VA or whether there is a more complicated explanation. Researchers also found that more than half of those with newly diagnosed breast, cervical, and ovarian cancers lived in the South compared with few (8%-13%) who lived in the Northeast.

The study findings were released in a poster at the 2023 annual meeting of the Association of VA Hematology/Oncology. Sarah Colonna, MD, study coauthor and medical director of breast oncology for the national VA, said in an interview that it is important to understand statistics regarding breast and gynecological cancer within the VA, especially as the system focuses more on patients with the conditions. And, she said, the wave of women who joined the military in recent decades are getting older and more likely to need oncology care. “We know women veterans are coming: They’re aging, and they’re going to get cancer.”

Colonna and colleagues examined statistics from the VA Corporate Data Warehouse to determine how many veterans were newly diagnosed with breast, uterine, ovarian, cervical, and vulvovaginal cancer in 2021 and 2022. The researchers compared their findings with 2020 statistics about the general population from the SEER database.

Within the VA, there were 3304 cases of breast cancer (mean age, 59 years; range, 23-99; mean body mass index [BMI], 31), 344 cases of cervical cancer (mean age, 46 years; range, 22-90; mean BMI, 29), 177 cases of ovarian cancer (mean age, 57 years; range, 24-80; mean BMI, 29), 365 cases of uterine cancer (mean age, 60 years; range, 24-85; mean BMI, 35), and 32 cases of vaginal/vulvar cancer (mean age, 56 years; range, 24-75; mean BMI, 31).

In contrast, the mean ages at diagnosis for the general population were slightly higher at 63 years for breast cancer, 50 years for cervical cancer, 63 years for ovarian cancer, and 63 years for uterine cancer. Vaginal/vulvar cancer was a bit of an outlier at mean age 69 years for the general population vs 56 years for the VA population; however, the number of cases in the latter group was quite low at 32 patients.

Overall, gynecological cancers were diagnosed at an average age of 55 years among the VA population vs 61 years among the general population. Men made up 11% of breast cancer cases in the VA vs 1% in the general population. “Of course, we have 10 times the proportion of men than in the outside,” said Colonna, an oncologist with the Huntsman Cancer Institute/Wahlen VA Medical Center in Utah. That may explain the difference, “but nobody knows for sure,” she said.

Patients Within the VA with the following cancers were more likely to be Black veterans than in the general population: breast, 30% vs 12%; cervical, 20% vs 14%; ovarian, 28% vs 10%; uterine, 25% vs 12%; and vaginal/vulvar, 44% vs 10%. This could reflect the fact that 30% of women treated within the VA are Black women vs 12% in the general population, Colonna said. Unfortunately, she said, “black women with breast cancer, tend to do really poorly. They tend to get it young, and they tend to die.”

As for the geographic distribution of cases, Colonna said it represents the high numbers of veterans who live in the South, suggesting that more VA oncology resources may be needed there.

In an interview, Aditi Hazra, PhD, MPH, an assistant professor of medicine at Harvard Medical School, said the new analysis is “very valuable”: “Women are a growing proportion of the veterans who serve, and we need more data to understand the risk factors and incidents of disease in this population.” Hazra said the next step will be to control the data for risk factors and “tease out what is driving the rates in the VA.”

There is no study funding, and the authors have no disclosures. Dr. Hazra discloses that she works for the VA and has collaborated with one of the study authors. 

CHICAGO—A new report offers a picture of patients seeking care for breast and gynecological cancers within the US Department of Veterans Affairs (VA) health care system: They are somewhat younger than their counterparts in the general population, and those with breast cancer are much more likely to be men.

            It is not clear whether these numbers are purely a reflection of the unique population within the VA or whether there is a more complicated explanation. Researchers also found that more than half of those with newly diagnosed breast, cervical, and ovarian cancers lived in the South compared with few (8%-13%) who lived in the Northeast.

The study findings were released in a poster at the 2023 annual meeting of the Association of VA Hematology/Oncology. Sarah Colonna, MD, study coauthor and medical director of breast oncology for the national VA, said in an interview that it is important to understand statistics regarding breast and gynecological cancer within the VA, especially as the system focuses more on patients with the conditions. And, she said, the wave of women who joined the military in recent decades are getting older and more likely to need oncology care. “We know women veterans are coming: They’re aging, and they’re going to get cancer.”

Colonna and colleagues examined statistics from the VA Corporate Data Warehouse to determine how many veterans were newly diagnosed with breast, uterine, ovarian, cervical, and vulvovaginal cancer in 2021 and 2022. The researchers compared their findings with 2020 statistics about the general population from the SEER database.

Within the VA, there were 3304 cases of breast cancer (mean age, 59 years; range, 23-99; mean body mass index [BMI], 31), 344 cases of cervical cancer (mean age, 46 years; range, 22-90; mean BMI, 29), 177 cases of ovarian cancer (mean age, 57 years; range, 24-80; mean BMI, 29), 365 cases of uterine cancer (mean age, 60 years; range, 24-85; mean BMI, 35), and 32 cases of vaginal/vulvar cancer (mean age, 56 years; range, 24-75; mean BMI, 31).

In contrast, the mean ages at diagnosis for the general population were slightly higher at 63 years for breast cancer, 50 years for cervical cancer, 63 years for ovarian cancer, and 63 years for uterine cancer. Vaginal/vulvar cancer was a bit of an outlier at mean age 69 years for the general population vs 56 years for the VA population; however, the number of cases in the latter group was quite low at 32 patients.

Overall, gynecological cancers were diagnosed at an average age of 55 years among the VA population vs 61 years among the general population. Men made up 11% of breast cancer cases in the VA vs 1% in the general population. “Of course, we have 10 times the proportion of men than in the outside,” said Colonna, an oncologist with the Huntsman Cancer Institute/Wahlen VA Medical Center in Utah. That may explain the difference, “but nobody knows for sure,” she said.

Patients Within the VA with the following cancers were more likely to be Black veterans than in the general population: breast, 30% vs 12%; cervical, 20% vs 14%; ovarian, 28% vs 10%; uterine, 25% vs 12%; and vaginal/vulvar, 44% vs 10%. This could reflect the fact that 30% of women treated within the VA are Black women vs 12% in the general population, Colonna said. Unfortunately, she said, “black women with breast cancer, tend to do really poorly. They tend to get it young, and they tend to die.”

As for the geographic distribution of cases, Colonna said it represents the high numbers of veterans who live in the South, suggesting that more VA oncology resources may be needed there.

In an interview, Aditi Hazra, PhD, MPH, an assistant professor of medicine at Harvard Medical School, said the new analysis is “very valuable”: “Women are a growing proportion of the veterans who serve, and we need more data to understand the risk factors and incidents of disease in this population.” Hazra said the next step will be to control the data for risk factors and “tease out what is driving the rates in the VA.”

There is no study funding, and the authors have no disclosures. Dr. Hazra discloses that she works for the VA and has collaborated with one of the study authors. 

TOPLINE:

Anti-acid drugs used by patients with systemic sclerosis reduce the bioavailability of mycophenolate mofetil (MMF).

METHODOLOGY:

• Researchers conducted an open-label, pragmatic crossover study of 20 patients (all female) with systemic sclerosis at a single center who were on a stable MMF dose (1.5-2 g/day) for the last 3 months or more.
• Participants sequentially took MMF alone for 1 month, then with the H2 receptor blocker (HRB) ranitidine 300 mg/day in the second month, then with the proton pump inhibitor (PPI) esomeprazole 40 mg/day in the third month.
• Researchers measured the bioavailability of MMF in the patients during treatment with ranitidine or esomeprazole and the impact of the drugs on the total GI score of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 instrument.
• Patients were excluded if they were receiving co-prescription of cholestyramine, magnesium- or aluminum-containing antacids, and rifampicin; taking prednisolone-equivalent dose > 5 mg/day; taking MMF plus a PPI or an HRB at baseline; living with chronic kidney disease with a glomerular filtration rate < 30 mL/min; positive for HIV, HCV, or HBV; or living with end-stage lung disease or gastroduodenal ulcers.

TAKEAWAY:

• Mean estimated 12-hour area under curve levels of mycophenolic acid dropped by 32.7% (mean difference = 22.28 mcg h mL–1) when patients added esomeprazole, and they dipped by 21.97% (mean difference = 14.93 mcg h mL–1) when they added ranitidine vs. MMF alone.
• The pharmacokinetic parameter T-max did not differ significantly between MMF alone vs. MMF plus ranitidine but was significantly different with esomeprazole. C-max significantly declined with administration of ranitidine or esomeprazole vs. MMF alone.
• Total GI scores dipped when patients added esomeprazole or ranitidine.

IN PRACTICE:

In patients with significant gastroesophageal reflux disease symptoms who need to take MMF, management options may include monitoring MMF drug levels, switching to enteric-coated mycophenolate sodium, and spacing doses with anti-acid drugs.

SOURCE:

Glaxon Alex, MD, and colleagues from the Center for Arthritis and Rheumatism Excellence in Kochi, India, conducted the study, which was published online in Seminars in Arthritis & Rheumatism.

LIMITATIONS:

The sample size is small, and the optimum dose of MMF is unknown.

DISCLOSURES:

The study had no outside funding. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Anti-acid drugs used by patients with systemic sclerosis reduce the bioavailability of mycophenolate mofetil (MMF).

METHODOLOGY:

• Researchers conducted an open-label, pragmatic crossover study of 20 patients (all female) with systemic sclerosis at a single center who were on a stable MMF dose (1.5-2 g/day) for the last 3 months or more.
• Participants sequentially took MMF alone for 1 month, then with the H2 receptor blocker (HRB) ranitidine 300 mg/day in the second month, then with the proton pump inhibitor (PPI) esomeprazole 40 mg/day in the third month.
• Researchers measured the bioavailability of MMF in the patients during treatment with ranitidine or esomeprazole and the impact of the drugs on the total GI score of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 instrument.
• Patients were excluded if they were receiving co-prescription of cholestyramine, magnesium- or aluminum-containing antacids, and rifampicin; taking prednisolone-equivalent dose > 5 mg/day; taking MMF plus a PPI or an HRB at baseline; living with chronic kidney disease with a glomerular filtration rate < 30 mL/min; positive for HIV, HCV, or HBV; or living with end-stage lung disease or gastroduodenal ulcers.

TAKEAWAY:

• Mean estimated 12-hour area under curve levels of mycophenolic acid dropped by 32.7% (mean difference = 22.28 mcg h mL–1) when patients added esomeprazole, and they dipped by 21.97% (mean difference = 14.93 mcg h mL–1) when they added ranitidine vs. MMF alone.
• The pharmacokinetic parameter T-max did not differ significantly between MMF alone vs. MMF plus ranitidine but was significantly different with esomeprazole. C-max significantly declined with administration of ranitidine or esomeprazole vs. MMF alone.
• Total GI scores dipped when patients added esomeprazole or ranitidine.

IN PRACTICE:

In patients with significant gastroesophageal reflux disease symptoms who need to take MMF, management options may include monitoring MMF drug levels, switching to enteric-coated mycophenolate sodium, and spacing doses with anti-acid drugs.

SOURCE:

Glaxon Alex, MD, and colleagues from the Center for Arthritis and Rheumatism Excellence in Kochi, India, conducted the study, which was published online in Seminars in Arthritis & Rheumatism.

LIMITATIONS:

The sample size is small, and the optimum dose of MMF is unknown.

DISCLOSURES:

The study had no outside funding. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Anti-acid drugs used by patients with systemic sclerosis reduce the bioavailability of mycophenolate mofetil (MMF).

METHODOLOGY:

• Researchers conducted an open-label, pragmatic crossover study of 20 patients (all female) with systemic sclerosis at a single center who were on a stable MMF dose (1.5-2 g/day) for the last 3 months or more.
• Participants sequentially took MMF alone for 1 month, then with the H2 receptor blocker (HRB) ranitidine 300 mg/day in the second month, then with the proton pump inhibitor (PPI) esomeprazole 40 mg/day in the third month.
• Researchers measured the bioavailability of MMF in the patients during treatment with ranitidine or esomeprazole and the impact of the drugs on the total GI score of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 instrument.
• Patients were excluded if they were receiving co-prescription of cholestyramine, magnesium- or aluminum-containing antacids, and rifampicin; taking prednisolone-equivalent dose > 5 mg/day; taking MMF plus a PPI or an HRB at baseline; living with chronic kidney disease with a glomerular filtration rate < 30 mL/min; positive for HIV, HCV, or HBV; or living with end-stage lung disease or gastroduodenal ulcers.

TAKEAWAY:

• Mean estimated 12-hour area under curve levels of mycophenolic acid dropped by 32.7% (mean difference = 22.28 mcg h mL–1) when patients added esomeprazole, and they dipped by 21.97% (mean difference = 14.93 mcg h mL–1) when they added ranitidine vs. MMF alone.
• The pharmacokinetic parameter T-max did not differ significantly between MMF alone vs. MMF plus ranitidine but was significantly different with esomeprazole. C-max significantly declined with administration of ranitidine or esomeprazole vs. MMF alone.
• Total GI scores dipped when patients added esomeprazole or ranitidine.

IN PRACTICE:

In patients with significant gastroesophageal reflux disease symptoms who need to take MMF, management options may include monitoring MMF drug levels, switching to enteric-coated mycophenolate sodium, and spacing doses with anti-acid drugs.

SOURCE:

Glaxon Alex, MD, and colleagues from the Center for Arthritis and Rheumatism Excellence in Kochi, India, conducted the study, which was published online in Seminars in Arthritis & Rheumatism.

LIMITATIONS:

The sample size is small, and the optimum dose of MMF is unknown.

DISCLOSURES:

The study had no outside funding. The authors report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

When I close my eyes and imagine what it is I do for a living, I see a computer screen.

I’m primarily a clinical researcher, so much of what I do is looking at statistical software, or, more recently, writing grant applications. But even when I think of my clinical duties, I see that computer screen.

The reason? The electronic health record (EHR) – the hot, beating heart of medical care in the modern era. Our most powerful tool and our greatest enemy.

The EHR records everything – not just the vital signs and lab values of our patients, not just our notes and billing codes. Everything. Every interaction we have is tracked and can be analyzed. The EHR is basically Sting in the song “Every Breath You Take.” Every click you make, it is watching you.

Researchers are leveraging that panopticon to give insight into something we don’t talk about frequently: the issue of racial bias in medicine. Is our true nature revealed by our interactions with the EHR?

We’re talking about this study in JAMA Network Open.

Researchers leveraged huge amounts of EHR data from two big academic medical centers, Vanderbilt University Medical Center and Northwestern University Medical Center. All told, there are data from nearly 250,000 hospitalizations here.

The researchers created a metric for EHR engagement. Basically, they summed the amount of clicks and other EHR interactions that occurred during the hospitalization, divided by the length of stay in days, to create a sort of average “engagement per day” metric. This number was categorized into four groups: low engagement, medium engagement, high engagement, and very high engagement.

courtesy Dr. F. Perry Wilson

courtesy JAMA Network Open

courtesy Centers for Disease Control and Prevention

F. Perry Wilson, MD, MSCE, is associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

When I close my eyes and imagine what it is I do for a living, I see a computer screen.

I’m primarily a clinical researcher, so much of what I do is looking at statistical software, or, more recently, writing grant applications. But even when I think of my clinical duties, I see that computer screen.

The reason? The electronic health record (EHR) – the hot, beating heart of medical care in the modern era. Our most powerful tool and our greatest enemy.

The EHR records everything – not just the vital signs and lab values of our patients, not just our notes and billing codes. Everything. Every interaction we have is tracked and can be analyzed. The EHR is basically Sting in the song “Every Breath You Take.” Every click you make, it is watching you.

Researchers are leveraging that panopticon to give insight into something we don’t talk about frequently: the issue of racial bias in medicine. Is our true nature revealed by our interactions with the EHR?

We’re talking about this study in JAMA Network Open.

Researchers leveraged huge amounts of EHR data from two big academic medical centers, Vanderbilt University Medical Center and Northwestern University Medical Center. All told, there are data from nearly 250,000 hospitalizations here.

The researchers created a metric for EHR engagement. Basically, they summed the amount of clicks and other EHR interactions that occurred during the hospitalization, divided by the length of stay in days, to create a sort of average “engagement per day” metric. This number was categorized into four groups: low engagement, medium engagement, high engagement, and very high engagement.

courtesy Dr. F. Perry Wilson

courtesy JAMA Network Open

courtesy Centers for Disease Control and Prevention

F. Perry Wilson, MD, MSCE, is associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

When I close my eyes and imagine what it is I do for a living, I see a computer screen.

I’m primarily a clinical researcher, so much of what I do is looking at statistical software, or, more recently, writing grant applications. But even when I think of my clinical duties, I see that computer screen.

The reason? The electronic health record (EHR) – the hot, beating heart of medical care in the modern era. Our most powerful tool and our greatest enemy.

The EHR records everything – not just the vital signs and lab values of our patients, not just our notes and billing codes. Everything. Every interaction we have is tracked and can be analyzed. The EHR is basically Sting in the song “Every Breath You Take.” Every click you make, it is watching you.

Researchers are leveraging that panopticon to give insight into something we don’t talk about frequently: the issue of racial bias in medicine. Is our true nature revealed by our interactions with the EHR?

We’re talking about this study in JAMA Network Open.

Researchers leveraged huge amounts of EHR data from two big academic medical centers, Vanderbilt University Medical Center and Northwestern University Medical Center. All told, there are data from nearly 250,000 hospitalizations here.

The researchers created a metric for EHR engagement. Basically, they summed the amount of clicks and other EHR interactions that occurred during the hospitalization, divided by the length of stay in days, to create a sort of average “engagement per day” metric. This number was categorized into four groups: low engagement, medium engagement, high engagement, and very high engagement.

courtesy Dr. F. Perry Wilson

courtesy JAMA Network Open

courtesy Centers for Disease Control and Prevention

F. Perry Wilson, MD, MSCE, is associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.

In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.

Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.

Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
 

Gender-sensitive approach

Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:

• Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
• Sex-specific differences in communication between male and female patients and between male and female physicians.

Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”

In contrast, women with axSpA exhibit the following differences:

• It is more likely for the cervical spine to be affected.
• Women are more likely to suffer from peripheral joint involvement.
• They suffer more from whole body pain.
• They have fatigue and exhaustion.  
• They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
• They are rarely HLA-B27 positive.

“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.

A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.

However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).

For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
 

TNF blockers

Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”

Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.

The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.

She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:

• Genetic, physical, or hormonal causes
• Widespread pain or fibromyalgia
• Late diagnosis or late application of therapy, which lowers the chances of remission.

Even the science itself has shown the following sex-specific shortcomings:

• Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
• Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
• Most of the data come from epidemiological analyses (not from basic research)
• Gaps in medical textbooks

Communication differences

Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:

• Describe their symptoms in terms of specifics
• Do not like to admit having mental health issues
• Are three to five times more likely to commit suicide because of depression than women

On the other hand, female patients behave in the following ways:

• Look for an explanation for their symptoms
• Often do not have their physical symptoms taken seriously
• Are often pushed in a psychosomatic direction.

Female physicians focus on the following questions:

• Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
• Psychosocial situations: consultations last 1 minute longer (10%).

Male physicians focus on the following questions:

• Medical history
• Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
• Diagnostics

Recognition and training

A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:

• 15% higher risk for a worse surgery result
• 16% higher risk for complications
• 11% higher risk for repeat hospitalization
• 20% higher risk for a longer period of hospitalization
• 32% higher risk for mortality

The study authors provided the following potential reasons for these differences:

• Male physicians underestimate the severity of symptoms in their female patients
• Women are less comfortable indicating their postoperative pain to a male physician
• Different working style and treatment decisions between female and male physicians
• Unconsciously incorporated role patterns and preconceptions

“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.

In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.

Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.

Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
 

Gender-sensitive approach

Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:

• Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
• Sex-specific differences in communication between male and female patients and between male and female physicians.

Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”

In contrast, women with axSpA exhibit the following differences:

• It is more likely for the cervical spine to be affected.
• Women are more likely to suffer from peripheral joint involvement.
• They suffer more from whole body pain.
• They have fatigue and exhaustion.  
• They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
• They are rarely HLA-B27 positive.

“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.

A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.

However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).

For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
 

TNF blockers

Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”

Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.

The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.

She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:

• Genetic, physical, or hormonal causes
• Widespread pain or fibromyalgia
• Late diagnosis or late application of therapy, which lowers the chances of remission.

Even the science itself has shown the following sex-specific shortcomings:

• Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
• Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
• Most of the data come from epidemiological analyses (not from basic research)
• Gaps in medical textbooks

Communication differences

Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:

• Describe their symptoms in terms of specifics
• Do not like to admit having mental health issues
• Are three to five times more likely to commit suicide because of depression than women

On the other hand, female patients behave in the following ways:

• Look for an explanation for their symptoms
• Often do not have their physical symptoms taken seriously
• Are often pushed in a psychosomatic direction.

Female physicians focus on the following questions:

• Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
• Psychosocial situations: consultations last 1 minute longer (10%).

Male physicians focus on the following questions:

• Medical history
• Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
• Diagnostics

Recognition and training

A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:

• 15% higher risk for a worse surgery result
• 16% higher risk for complications
• 11% higher risk for repeat hospitalization
• 20% higher risk for a longer period of hospitalization
• 32% higher risk for mortality

The study authors provided the following potential reasons for these differences:

• Male physicians underestimate the severity of symptoms in their female patients
• Women are less comfortable indicating their postoperative pain to a male physician
• Different working style and treatment decisions between female and male physicians
• Unconsciously incorporated role patterns and preconceptions

“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.

In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.

Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.

Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
 

Gender-sensitive approach

Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:

• Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
• Sex-specific differences in communication between male and female patients and between male and female physicians.

Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”

In contrast, women with axSpA exhibit the following differences:

• It is more likely for the cervical spine to be affected.
• Women are more likely to suffer from peripheral joint involvement.
• They suffer more from whole body pain.
• They have fatigue and exhaustion.  
• They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
• They are rarely HLA-B27 positive.

“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.

A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.

However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).

For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
 

TNF blockers

Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”

Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.

The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.

She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:

• Genetic, physical, or hormonal causes
• Widespread pain or fibromyalgia
• Late diagnosis or late application of therapy, which lowers the chances of remission.

Even the science itself has shown the following sex-specific shortcomings:

• Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
• Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
• Most of the data come from epidemiological analyses (not from basic research)
• Gaps in medical textbooks

Communication differences

Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:

• Describe their symptoms in terms of specifics
• Do not like to admit having mental health issues
• Are three to five times more likely to commit suicide because of depression than women

On the other hand, female patients behave in the following ways:

• Look for an explanation for their symptoms
• Often do not have their physical symptoms taken seriously
• Are often pushed in a psychosomatic direction.

Female physicians focus on the following questions:

• Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
• Psychosocial situations: consultations last 1 minute longer (10%).

Male physicians focus on the following questions:

• Medical history
• Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
• Diagnostics

Recognition and training

A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:

• 15% higher risk for a worse surgery result
• 16% higher risk for complications
• 11% higher risk for repeat hospitalization
• 20% higher risk for a longer period of hospitalization
• 32% higher risk for mortality

The study authors provided the following potential reasons for these differences:

• Male physicians underestimate the severity of symptoms in their female patients
• Women are less comfortable indicating their postoperative pain to a male physician
• Different working style and treatment decisions between female and male physicians
• Unconsciously incorporated role patterns and preconceptions

“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.